Primary failure of eruption (PFE) is a rare oral disease with an incidence rate of 0.06%. It is characterized by abnormal eruption mechanisms that disrupt tooth eruption. The underlying pathogenic genetic variant and mechanism of PFE remain largely unknown. The purpose of this study was to explore the role of a novel transmembrane protein 119 (TMEM119) mutation in two PFE patients in a Chinese family. Information collection was performed on the family with a diagnosis of PFE, and blood samples from patients and healthy family members were extracted. Whole-exome sequencing was performed. Bioinformatics analysis revealed that a heterozygous variant in the TMEM119 gene (c.G143A, p.S48L) was a disease-associated mutation in this family. Recombinant pcDNA3.1 plasmid-containing wild-type and mutant TMEM119 expression cassettes were successfully constructed and transfected into MC3T3-E1 cells, respectively. The results of in vitro analysis suggested that the subcellular distribution of the TMEM119 protein was transferred from the cell cytoplasm to the nucleus, and the ability of cells to proliferate and migrate as well as glycolytic and mineralized capacities were reduced after mutation. Furthermore, rescue assays showed that activating transcription factor 4 (ATF4) overexpression rescued the attenuated glycolysis and mineralization ability of cells. Results of in vivo analysis demonstrated that TMEM119 was mainly expressed in the alveolar bone around the mouse molar germs, and the expression level increased with tooth eruption, demonstrated using immunohistochemistry and immunofluorescence. Collectively, the novel TMEM119 mutation is potentially pathogenic in the PFE family by affecting the glucose metabolism and mineralized function of osteoblasts, including interaction with ATF4. Our findings broaden the gene mutation spectrum of PFE and further elucidate the pathogenic mechanism of PFE.

Purpose: Research on primary maxillary central incisors (PMCIs) remains limited, and their morphological variations have rarely been documented. This study aimed to reconstruct anatomy of PMCIs in children from Beijing (China) and to analyse their commonalities and variations. Methods: Employing a threshold-based semi-automated region segmentation method, anatomical models of 101 PMCIs were reconstructed from existing cone-beam computed tomography (CBCT) images. Models were classified according to the Vertucci classification. For each variant type, representative morphological parameters of the hard tissue, pulp chamber, and canals were measured. The type with the highest prevalence was selected as the main type and its average model was constructed, representing the most common characteristics of PMCIs. Results: All PMCIs had a single root, whereas novel canal variations were identified. The most common canal type was Type I (61.4%), followed by Type V (20.8%) and Type III (17.8%). Anatomical parameters of main-type PMCIs were as follows: hard-tissue length = 15.76 ± 0.89 mm; pulp chamber and canal length = 12.94 ± 1.15 mm; and apical labial curvature angle was 22.57°. Statistical analysis indicated no differences between left and right, and no sex-related differences (p > 0.05). Statistically significant differences between the main-type and other variants were noted for several pulp-chamber and canal measurements (p < 0.05), but not for hard-tissue measurements (p > 0.05). An average main-type model was constructed; its inner and outer profiles conformed to the general characteristics of main-type PMCIs. Conclusion: PMCI canal variations were more complex than previously recognised, with uniform hard-tissue anatomy. Furthermore, an average main-type model was constructed, as a potentially valuable tool for dental education.